Previous editions of Research Round-Up: Three, Two, One
Welcome to the latest edition of Research Round-Up! If you’ve missed previous editions and want to know what’s happening in the world of EDS research, click the links above.
This month, we’re doing something a little different. Instead of individually discussing some recent research articles, we’re taking a deep dive into one topic: the possible connection between EDS and neurodivergent conditions like autism and attention hyperactivity attention disorder. There has been a lot of talk about the overlaps in symptoms and questions about whether the conditions are related. Below is a summary and explanation of most of the research that has been done on the connection between EDS/joint hypermobility and neurodivergent conditions. Read on, and get ready to learn!
Language and how we use it to describe ourselves is one of the great joys of being able to communicate. Language preferences in terms of disability representation differ widely within our community, so we are doing our best to be as sensitive as we can. As always, if you have feedback, please leave a comment or send an email.
Though case studies have existed since the 1980s, research into the connection between Ehlers-Danlos syndrome (EDS) and other joint hypermobility-related conditions, such as hypermobility spectrum disorder (HSD), Marfan syndrome, and Loeys-Dietz syndrome, and neurodivergence has become a hot topic in recent years. Current studies investigate the connection between various neurodivergent conditions, most often autism (ASD) and attention deficit hyperactivity disorder (ADHD) and EDS, joint hypermobility, pain, fibromyalgia, dysautonomia, and more. Below is a compilation of information from research articles from the last 15 years.
Please note: these are not medical recommendations. We are not doctors, so ask your doctor what’s right for you.
Before you read, you might be interested in:
What is neurodiversity?
What is autism?
What is sensory sensitivity?
Shared Symptomology
When doctors and researchers looked into the symptoms of people with joint hypermobility (which includes GHJ, BJH, HSD, hEDS, and all types of EDS) and those with neurodivergent conditions (mostly with ASD and ADHD), they found a number of similar symptoms. Here are some of them, in no particular order:
- Sensory hypersensitivity (which may be diagnosed separately as sensory processing disorder)
- Motor development delays, difficulty with coordination, and impaired proprioception
- Psychiatric conditions, such as anxiety, depression, bipolar disorder, eating disorders, and suicidal behavior
- Sleep disturbances, including insomnia, sleep-related anxiety, hypersomnia (also known as excessive daytime sleepiness), periodic limb movement, daytime fatigue, and more
- Autonomic dysfunction, including POTS, orthostatic intolerance, and dysregulation
- Gastrointestinal issues (GI), like constipation, diarrhea, gastroparesis, irritable bowel syndrome, and more. Some GI disorders are thought to be related to autonomic dysfunction.
- Chronic pain, mainly musculoskeletal but also including headaches and visceral pain. In addition to chronic pain, shared symptoms also include hypersensitivity to pain, pain-related behavioral changes, and increased sensitivity to discomfort
- Learning disorders, sometimes thought to be connected to impairments in proprioception, “which alters coordination and posture and likewise may be involved in the acquisition of verbal communication and motor competence” (Piedimonte et al. 2018)
- Connective tissue abnormalities, such as impaired collagen synthesis, ptosis (upper eyelid droopiness), flat feet, and altered proprioception
- Endocrine dysregulation such as polycystic ovarian syndrome, maternal diabetes, and others
- Gynecological symptoms, such as sensitivity to hormonal fluctuations and an increase in symptom severity during puberty, prior to menstruation, during the postpartum period, and when on oral contraception. People with female reproductive systems who were diagnosed with ASD and GJH reported higher instances of endometriosis, dysmenorrhea (three times as much as those without GJH), and severe teen acne than those with ASD only (Casanova et al. 2018).
- Immune dysregulation, including mast cell activation/dysregulation, which is common in both people with EDS and those with ASD. People with hypermobility and ASD had higher rates of autoimmune disorder.
- Epilepsy is found seven times more in autistic people than in the general population. Seizure disorders have been reported in EDS, especially in certain subtypes such as “an EDS-like disorder associated with mutations in the FLNA gene… [that] presents with periventricular heterotopias, a structural anomaly that has also been noted in autism” (Casanova et al. 2020).
A Constellation of Possible Causes
There are several theories as to why the overlap between EDS/joint hyoermobility and neurodivergent conditions may exist. None of the following theories have been proven, but researchers are focusing on the following areas:
Genetic factors
One theory is that the overlap between joint hypermobility and neurodivergent conditions is caused by genetics. According to Casanova (2020), “Genetic data indicate similarities at the molecular, cellular, and tissue levels, as illustrated by numerous genetic syndromes with [co-occurence of] autism and hypermobility.” Ptosis, flat feet, and the use of orthodontic appliances—possibly because of a connective tissue disorder—may be significant and overlap with specific neurodivergent disorders.
Another study suggests that joint hypermobility and autism may come from the same genetic background but are expressed differently in different people. Additionally, the symptoms of both connective tissue disorders and neurodivergent conditions can be seen in other family members when one or both conditions have been diagnosed in a single family member.
Connective Tissue Abnormalities and Brain Structure
Another theory rests on the impaired collagen synthesis caused by Ehlers-Danlos syndrome. The nervous system contains collagen, and defective collagen could affect brain structures like the corpus callosum, which communicates between the hemispheres. Collagen abnormalities can also impair neural connections and white matter, which are important for controlling attention and cognitive processing.
Researchers have observed structural differences in the brain between people with and without joint hypermobility in four areas. One of these is the amygdala, which is responsible for processing emotions (often fear, anxiety, and aggression) as well as memory consolidation. Another is the anterior cingulate cortex, which is responsible for a number of cognitive and emotional processes, such as decision-making, emotional regulation, pain processing, attention, and motivation. The third is the parietal lobe, which handles sensory integration, bodily representation, and spatial awareness (like proprioception). Lastly, people with joint hypermobility have less superior temporal volume, an area mainly used for processing auditory information. If the volume of this part of the brain is abnormal, it can cause schizophrenia, social anxiety disorders, and language problems.
Autistic people also show differences in their amygdala and superior cortex structure (which includes the parietal lobe). The structural brain changes associated with joint hypermobility echo some of the signs of ASD.
One study also looked at how common hEDS/HSD-like symptoms were in people with functional neurological disorders (FNDs), people with ASDs who did not have intellectual disabilities, and a group of people who were not diagnosed with any conditions. These self-reported questionnaires showed that people with FNDs and ASDs have higher rates of hEDS/HSD-like symptoms. The overlap of symptoms between FNDs, ASDs, and EDS might not be the end of the story. EDS may make the symptoms of FNDs and ASDs worse.
When these structural changes happen, executive function and motor coordination get worse. This leads to problems like not paying attention, acting on impulse, and being restless with their movements, which are similar to symptoms seen in people with ADHD.
Maternal Immune System
Newer studies have found that the mother’s immune system may influence whether her child develops EDS/HSD and/or autism. Researchers have found that 20% of women with joint hypermobility report having autistic children, which is similar to the rate at which autistic women have autistic children. Additionally, if a child in the study has autism, it is likely that their mother has more severe immune disorders. This may have to do with the number of cytokines and chemokines a mother produces during pregnancy. Those with higher amounts produce autistic children and intellectual disabilities, while women with lower amounts produce autistic children but no intellectual disabilities. Various immunomodulators and autoantibodies have a direct effect on embryonic and fetal brain development, so it’s not out of the question that these events might be linked.
Personal Immune System
Aside from the disruption of brain development we talked about above, there have been suggestions that problems with the immune system that are linked to EDS may be the link between EDS and neurodivergent conditions. Research has shown that there is immunological dysfunction in ASD and mast cell dysregulation in EDS, suggesting both conditions have immune system dysregulation. This is only a suggestion; there has been no link established showing the immune system of a person with EDS or a neurodivergent disorder causing the other condition.
Autistic people tend to have troubles with their immune systems, like allergies, autoimmune conditions, and sensitivities to medications and chemicals, to name a few. This has encouraged researchers to look at the transforming growth factor beta (TGF-β) pathway. TGF-β is an important messenger that helps cells talk to each other and control many things, like how tissues are built and how the immune system works. In Marfan Syndrome (MS), another connective tissue disorder related to EDS, there is a problem with a protein called fibrillin. One of fibrillin’s jobs is to keep the TGF-β under control by creating a storage space for the latent TGF-β binding protein (LTBP). If fibrillin is defective, the LTBP can get out of control, causing immune system dysregulation.
Some people with hypermobile EDS have features of Marfan syndrome, such as long limbs, long toes and fingers, deep-set eyes, a small jaw, and flat cheekbones, to name a few. This suggests that the TGF-β pathway might be involved in hEDS, the one type of EDS without a definite genetic cause. Since it also connects tissue building and its components, like collagen, to the immune system, dysregulation in this pathway can cause “issues with the tissues.”
Same studies have found low levels of the TGF-β1 (a form of TGF-β) in autistic people, which they theorize may lead to some of the problems with the immune system experienced by autistic people. This leads researchers to believe this TGF-β pathway is a prime area of future research into the possible connection between the immune system, connective tissue disorders, and autism.
Additionally, fibrillin is one component of the extracellular matrix (ECM). Fibrillin forms microfibrils, which create a scaffolding for collagen to build upon. If the fibrillin is dysregulated, as described above, the collagen won’t have strong microfibrils to build upon, making the extracellular matrix weaker. If there is a defect in collagen as well (as in EDS and Marfan), this could lead to more answers about how the extracellular matrix is involved in EDS.
Endocrine Dysregulation
There is a growing area of research that is looking into whether endocrine disruption can be considered an origin of ASD. A recent study found that women with ASD and joint hypermobility self-reported more immune- and endocrine-related conditions than those with ASD but without joint hypermobility.
Additionally, dopamine dysfunction is common in ADHD and hEDS. The dopamine pathways are crucial for motor control, attention, and controlling impulsivity, as seen in people with ADHD. Imbalances of dopamine in people with hEDS can lead to motor deficits, cognitive challenges, and emotional dysregulation. This neurobiological pathway might be disrupted, which could help explain the link between hEDS and ADHD, which can also include issues with controlling impulses, paying attention, and performing complex tasks. Endocrine disruption and how it affects the immune system continue to be an area of research for both autism and EDS.
Some metabolites of estrogen may also play a role in connective tissue disorders and their related symptoms. These metabolites stop the skin from making collagen or speed up the breakdown of collagen in tendons and ligaments. Estrogen is also a major immunomodulator and plays a role in stimulating mast cell degranulation. Estrogen can be implicated in connective tissue disorders and their symptoms, which may explain why more women are diagnosed with EDS. There are, anecdotally, also more women presenting with neurodivergent conditions and joint hypermobility-related conditions, so estrogen and its effect on the brain and connective tissues is an area ripe for research.
Autonomic Dysfunction & Proprioceptive Awareness
“Hypermobile individuals have greater exteroception (sensitivity to the environment), nociception (sensitivity to pain) and somatosensory amplification [while] also experiencing decreased proprioception (perception of position of own body)” (Ryan et al., under review). These traits are also found in people diagnosed with ASD and ADHD and are related to the dysfunction of the autonomic nervous system. The proprioceptive impairment may be one answer to the connection between neurodivergent conditions and EDS/HSD. Proprioception assists in coordination and posture and can be involved in learning to talk and walk. If proprioception is impaired by hypermobile joints, people with joint hypermobility-related conditions may show delays in walking, talking, and other signs that look similar to some neurodivergent conditions.
Many researchers think that the amount of executive function needed to keep motor control when proprioception is low may be too much for the part of the brain that handles executive function, which can cause ADHD symptoms like drowsiness, lack of focus, memory loss, and more. It makes sense that these symptoms could then affect cognitive, behavioral, and motor skills as well as some parts of neurodevelopment. This could start a cycle of symptoms that could be seen as ASD, ADHD, or EDS/HSD. Autonomic dysfunction, like POTS, and pain can also amplify ADHD-like symptoms like inattention, hyperactivity, fatigue, and anxiety. Mood disorders and anxiety are strongly linked with autonomic dysfunction and could be related to variations in energy levels and chronic fatigue, more shared symptomology between neurodivergent conditions and joint hypermobility-related conditions.
Pediatric Populations: Symptoms and Screening
One obvious place to start when considering a child’s likelihood of having EDS/HSD, another joint hypermobility or connective tissue-related condition, or a neurodivergent condition is to look at family genetics. Children with parents who have these conditions are more likely to develop them, especially EDS and autism. A genetic counselor is the best person to see in this situation.
Many of the same symptoms seen in adults with both EDS/HSD/joint hypermobility and a neurodivergent condition will be present in children. It’s also important to look at developing motor, verbal, cognitive, and behavioral skills. For example, low muscle tone, joint laxity, clumsiness, apraxia (difficulty with skilled movement despite ability and desire), sleep disturbances, and toe-walking have been common findings in autistic people. They can also be present in hypermobility-related disorders. Many children who have both ADHD and EDS present with learning disorders in comparison to children without either condition.
Neuropsychiatry and psychology departments are different from those that diagnose and treat musculoskeletal disorders, including primary care and genetics. This means that it is unlikely that a possible overlap between disorders affecting connective tissues and hypermobile joints and neurodivergent conditions would be found by accident. The parent or guardian can choose to have their child screened in the other department, but they may want to wait to see if overt or extensive signs or symptoms of the other condition are present. A screening for EDS/HSD may help autistic people, who may be in pain but unable to communicate it, have the pain assessed appropriately. Csecs et al. (quoted in Ryan et al., under review) found that musculoskeletal pain is the most common pain reported among people with neurodivergent conditions. If joint hypermobility or a connective tissue disorder is found, it is more likely that pain will be assessed and treated appropriately.
Additionally, if autism is found in a person with EDS, HSD, or a related condition, it can receive the proper attention rather than the symptoms being dismissed as part of the autism diagnosis. As Baeza-Velasco et al. said, “[m]ental-health-related stigma can prevent more [in-]depth investigations into an underlying cause of systemic complaints, the exacerbation of behavioral problems, and/or comorbid [neurodivergent disorders]” (2018).
Study Limitations to Consider
Not every study can cover everything. Inevitably, studies will need to exclude certain criteria, narrow down their focus, and ultimately exclude some methods, theories, and data. It doesn’t make the study wrong or bad; every breakthrough needs to start somewhere. If a study lists limitations or areas of further research, it tells other researchers where to start when continuing the investigation.
While the studies included here have many intriguing findings, the research into the connections between EDS/HSD/joint hypermobility and neurodivergent conditions is just at the beginning, so there will be some limitations. Here are the ones these studies shared.
- Confounding variables: In cause-and-effect studies, confounding variables refer to external factors that can influence both the cause and sometimes the effect.
- Less-than-ideal participant randomization
Participants who self-select
Results in one population cannot always be applied to another (e.g., results from studies on women can’t always be applied to men, results from children can’t always be applied to adults, studies on hEDS can’t always be applied to kEDS, etc.) - Small sample sizes
- Inconsistent diagnoses, measurements, and physical exams
- Bias and memory lapses in participants when using self-reported surveys
- Inaccurate or out-of-date medical records and billing information
- Bias in researchers (e.g. the researcher isn’t blinded to study groups)
Conclusion
It’s doubtful that, at the beginning of the twentieth century, Henri-Alexandre Danlos and Edvard Ehlers would have dreamed that their “skin and joints” condition would someday be explored by neuroscientists, geneticists, and other scientists for a connection to brain development and related conditions. What will the research for a link between neurodivergent conditions and EDS/HSD and other connective tissue and joint hypermobility-related conditions show? We have a preview here, and if this is just a spark, the fire will soon follow, hopefully providing answers to our burning questions.
Language preferences in terms of disability representation differ widely within our community, so we are doing our best to be as sensitive as we can. Furthermore, please remember, this isn’t medical advice. Share this information with your doctors to discuss what steps might be right for you. This research has shown many interesting possibilities, but none of this has been proven yet. As always, if you have feedback, please leave a comment or send an email.
Sources consulted
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Written and researched by Kate Schultz
February 2025
